Adv Ther (2021) 38:2114–2129

https://doi.org/10.1007/s12325-021-01692-z

REVIEW

A Review of Robotic and OCT-Aided Systems

for Vitreoretinal Surgery
Elan Z. Ahronovich . Nabil Simaan . Karen M. Joos

Received: January 18, 2021 / Accepted: February 27, 2021 / Published online: April 3, 2021
Ó The Author(s) 2021

ABSTRACT systems, and (4) magnetic guidance robots. This

review covers the improvements and the
The introduction of the intraocular vitrectomy remaining needs for safe, cost-effective clinical
instrument by Machemer et al. has led to deployment of robotic systems in vitreoretinal
remarkable advancements in vitreoretinal sur- surgery.
gery enabling the limitations of human physi-
ologic capabilities to be reached. To overcome
the barriers of perception, tremor, and dexter- Keywords: Image-guided surgery; Medical
ity, robotic technologies have been investigated robotics; Micromanipulator; Ophthalmic
with current advancements nearing the feasi- surgery; Ophthalmology; Optical coherence
bility for clinical use. There are four categories tomography; Telemanipulation; Vitreoretinal
of robotic systems that have emerged through surgery
the research: (1) handheld instruments with
intrinsic robotic assistance, (2) hand-on-hand
robotic systems, (3) teleoperated robotic

E. Z. Ahronovich
Advanced Robotics and Mechanism Applications
(ARMA) Laboratory, Department of Mechanical
Engineering, Vanderbilt University, Nashville, TN
37235, USA

N. Simaan
Advanced Robotics and Mechanism Applications
(ARMA) Laboratory, Department of Mechanical
Engineering, Department of Computer Science,
Vanderbilt University, Nashville, TN 37235, USA
e-mail: nabil.simaan@vanderbilt.edu

K. M. Joos (&)
Vanderbilt Eye Institute, Vanderbilt University
Medical Center, Nashville, TN 37232, USA
e-mail: karen.joos@vumc.org

K. M. Joos
Department of Biomedical Engineering, Vanderbilt
University, Nashville, TN 37235, USA
Adv Ther (2021) 38:2114–2129
Key Summary Points
To overcome the barriers of perception,
tremor, and dexterity in vitreoretinal
surgery, robotic technologies have been
investigated with current advancements
nearing the feasibility for clinical use.
There are four categories of robotic
systems that have emerged through the
research: (1) handheld instruments with
intrinsic robotic assistance, (2) hand-on-
hand robotic systems, (3) teleoperated
robotic systems, and (4) magnetic
guidance robots.
The future of vitreoretinal surgery may
include some of the robotic systems or
implementations of technology
introduced in the development of the
robots.
Limitations of surgical robots include
barriers presented by sensor-actuation lag
that can be limited by using high
sampling frequencies. Also, heavy
computational demands from visual
feedback technologies currently make
real-time integration challenging.
Clinical surgical robotics will likely use
technologies such as optical coherence
tomography and tool tip force
measurements to add accuracy.
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INTRODUCTION
Needs and Challenges in Ophthalmic
Surgery
Despite vast advances in vitreoretinal surgery
since Machemer et al. [1], it presents challenges
to surgeons in terms of precision, perception,
and manipulation dexterity. A typical setup
during these procedures involves multiport
access into the vitreous cavity with thin tools
(e.g., picks, graspers, light source). Visualization
of the retina through a surgical microscope is
achieved through the pupil with adding a
focusing lens on or above the cornea. Surgeons
have to stabilize the eye while operating one to
two instruments within the vitreoretinal space.
Surgical tools generally lack distal dexterity
owing to their small size (generally less than
900 lm in diameter) and they have to be
maneuvered under deficient perception condi-
tions. For example, the visualization of the
anatomy is limited through a dilated iris, espe-
cially if dilation is poor. Tool shadows are hard
to perceive because of complex lighting condi-
tions with chandelier illumination or a small
moving endoilluminator light held in the sur-
geon’s second hand and the retinal anatomy
presents semitransparent features (e.g., retinal
membrane) that can be difficult to see. Added to
these challenges is the difficulty of measuring
tool tip interaction forces because of the inter-
ference from tool–trocar friction forces as con-
cluded by Jagtap et al. [2]. Further, Jensen et al.
[3] showed that the delicate anatomy of the
retina can apply reaction forces less than
7.5 mN for 77% of the duration of a vitreoreti-
nal procedure which was perceived by the sur-
geon only 20% of the time. This review
describes current retinal surgical limitations,
the parallel developments of optical coherence
tomography (OCT) and surgical robotics, and
the intersection of the two technologies which
have the potential to revolutionize patient care.
Success of many vitreoretinal procedures
depends on safe manipulation of the delicate
anatomy of the retina. For example, epiretinal
membrane peeling requires careful peeling of a
layer that can be on average 61 ± 28 lm thick
2116
[4] while avoiding trauma to the underlying
retinal anatomy. Treatment of retinal detach-
ments requires maneuvers using picks and
miniature graspers/cutters while avoiding exac-
erbating the retinal detachment and avoiding
inadvertent touching of the lens or causing
retinal hemorrhage. Previous experimental
characterizations of physiologic tremors illus-
trate the challenge of accomplishing such pre-
cise tasks. For example, the average root mean
square (rms) amplitude of tremor with a four-
subject user study ranged between 14 and
142 lm [5] when holding a tool still and
between 59 and 341 lm when actuating a
microsurgical grasper. In another example
Singh and Riviere [6] tracked the tool motion
during epiretinal membrane peeling and repor-
ted the rms amplitude of tremor at 38 lm for a
single-subject study. These reported magnitudes
of tool tremor are large enough to make
microretinal procedures exceedingly challeng-
ing. To overcome tremor, four approaches using
robotics were considered in the literature. In the
first method, a handheld miniature robotic
platform was used for tremor cancellation of
tracked instruments. Examples of this approach
include Riviere et al.’s Micron [7], Song et al.’s
SMART OCT-based device [8], and Cheon et al.’s
OCT-guided depth-locking handheld microin-
jector [9]. In the second method, a hand-on-
hand approach is used where the surgical
instrument is held by a robot and the surgeon’s
hand. Forces by the surgeon’s hand are used to
command the robot (tool) motion while also
providing tremor filtration, Taylor et al.’s
Steady-Hand eye robot [10] for example. A third
approach using telemanipulation with a sur-
geon controlling a robotically guided surgical
tool via a control station detached from the
robot was initially explored by Charles [11], Wei
et al. [12], Yu et al. [13], and Meenink et al. [14].
Finally, the fourth approach using extraocular
magnetic fields achieves manipulation of two
types of intraocular robots. Kummer et al. [15]
demonstrated intraocular microcapsule robots
and Charreyron et al. [16, 17] demonstrated
steerable magnetic-tipped catheters for drug
injection delivery and retinal vein cannulation.
Vitreoretinal surgery is also complicated by
perception barriers owing to operating through
Adv Ther (2021) 38:2114–2129
a microscope and due to limited tactile feed-
back. Typically, humans rely on a tactile
response as a form of confirmation of contact-
ing an intended target when performing a task
such as surgery. However, the delicate intraoc-
ular anatomy does not produce reaction forces
great enough to overcome the friction between
a surgical tool and trocar to reach a level per-
ceptible to humans. With this lack of tactile
feedback, surgeons are forced to rely heavily on
visual cues to discern tool proximity and con-
tact of the surgical tools with the anatomy [3].
However, intraocular visualization via a surgical
microscope has limits of useful depth percep-
tion and the visible field of view is restricted by
the dilated iris. In addition to manipulating
instruments inside the eye, surgeons may also
tilt the eye under the microscope. In some cases,
the target anatomy is difficult to visualize using
white-light imaging. For example, epiretinal
membranes are mostly transparent which stan-
dard light microscopes are incapable of visual-
izing without the addition of a steroid
suspension or indocyanine green (ICG) to stain
the membranes. Surgeons may also use endo-
scopes for auxiliary peripheral visualization;
however, these scopes have limited resolutions
compared to current microscopes. To address
the challenge of depth perception, previous
investigations have augmented instruments
with OCT probes. For example, Balicki et al. [18]
used an A-scan OCT probe to maintain the
distance of a robotic-controlled tool tip from
retinal anatomy. Yu et al. [19, 20] used forceps
integrated with a B-mode OCT probe for depth
perception feedback. In Yu et al. [19] it was
shown that OCT feedback improved depth
perception and success of approaching a surface
and peeling a surface membrane.
In addition to precision and perception
challenges, there are challenges due to rigid
instrumentation offering limited maneuver-
ability. Vitreoretinal surgical tools are generally
slender instruments with rigid shafts. These
instruments are constrained to the traditional
four-DOF (degrees of freedom) motions avail-
able to minimally invasive instruments (tilt in
two directions and rotation about and transla-
tion along the longitudinal axis of the tool). As
a result, the tool tip dexterity of these
Adv Ther (2021) 38:2114–2129
instruments is quite limited. One can reach a
particular site, but with limited control of tool
tip orientation. Surgeons have to carry out sur-
gical maneuvers of lifting membranes with
picks and graspers despite their limited distal tip
dexterity and contend with the need for
bimanual manipulation in order to stabilize the
eye while operating tools inside it. Ikuta et al.
[21] proposed the use of manual active bending
forceps, but the current clinical repertoire of
surgical forceps still remains predominantly
without active distal bending. The four scenar-
ios of ocular and intraocular manipulation have
been considered [22] with an emphasis on
quantifying the possible benefits of instrumen-
tation with intraocular dexterity. It was shown
that adding a single DOF of bending sideways
can increase orientational dexterity, compared
to rigid instruments, by 31.6% and 57.7% for
translational and rotational manipulation,
respectively. Several tools and robotic instru-
ments have been considered to overcome the
problem of intraocular dexterity. In Simaan
et al. [23] the concept of intraocular dexterity
tools using continuum bending cannulas was
introduced and later implemented by Wei et al.
[12, 24] and Yu et al. [13]. He et al. [25] intro-
duced a prototype of a 0.9 mm handheld con-
tinuum robot offering intraocular dexterity that
was later integrated with a robotic platform by
Song et al. [26].
The aforementioned challenges of tremor,
limited visual and tactile perception, and tool
tip dexterity can be alleviated in several ways.
For example, active tools can limit the effects of
human tremor to increase surgical precision by
filtering sensor input to produce tremorless
actuator control. Visual perception can be aug-
mented using OCT to obtain cross-sectional
imaging of tissue yielding a richer set of infor-
mation of target anatomy. Using sensors that
can detect forces imperceptible to humans
enhances a surgeon’s effective tactile percep-
tion. For higher dexterity, continuum segment
tools offer higher ranges of motion with
manipulation directly by a surgeon or attached
to robotic systems for greater levels of manipu-
lability and accuracy. In the following we dis-
cuss some of the tools that have been developed
to address the three main areas outlined above
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limiting vitreoretinal surgery and discuss
prospective areas of development to further
lessen these constraints.
METHODS TO IMPROVE
VISUALIZATION: OPTICAL
COHERENCE TOMOGRAPHY (OCT)
OCT is a standard diagnostic and surgical
planning ophthalmic tool that can develop
cross-sectional images of tissue using light
reflectance. Dayani et al. used a handheld
device during planned surgical procedure
interruptions [27]. Binder et al. first used a
microscope-mounted unit following surgical
manipulations [28]. The Duke [29–38], Cleve-
land Clinic/Case Western Reserve [36, 39–47],
Vanderbilt [48], and international groups
[28, 49–52] developed improvements for the
microscope-mounted intraoperative OCT sys-
tems with commercial US Food and Drug
Administration (FDA)-approved systems avail-
able for the operating room [53].
Non-OCT surgical intraocular endoscopes
are FDA-approved [54–60], but there is not yet
an approved facile ophthalmic OCT probe to
enable peripheral retina visualization as well as
bypass corneal and lenticular opacities that may
hinder direct central visualization [61]. Iftimia
et al. [62] developed an A-scan 250 lm OCT
probe for one-dimensional measurement of
tissue.
Balicki et al. [18] reported an intraocular
common path A-scan OCT probe. A 20-gauge
coplanar probe was developed which success-
fully guided the depth of mid-infrared laser
incisions of the retina [63]. The OCT-imaging
component alone was housed within a 25-gauge
tube which was readily amenable to imaging
through the more recent 23-gauge and 25-gauge
trocars preferred for contemporary retinal surg-
eries [64]. Addition of a needle [65] or forceps
[19] increased the size only to 23 gauge. This
OCT probe has been added to robotic platforms
described in the following section.
Ray et al. presented a custom mount that
attached the Bioptigen handheld probe to an
ophthalmic surgical microscope [66]. OCT
images from 24 patients undergoing macular
2118
hole or epiretinal membrane surgery were ana-
lyzed with subsequent quantitative measure-
ment of geometry and retinal thickness
providing insight into the anatomical changes
in the retina resulting from macular surgery and
verifying surgery completion. The feasibility
and safety of microscope-mounted OCT in
prospectively and retrospectively enrolled eyes
during several ophthalmic surgeries was repor-
ted, and it enhanced surgeons’ understanding
of the underlying anatomy in more than 40% of
the cases during lamellar keratoplasty and reti-
nal membrane peeling [67–69].
Microscope-integrated systems have been
developed which combine the OCT and surgical
microscope optical paths to enable imaging
simultaneously with surgical maneuvers
[30, 31, 41, 42, 70, 71]. The Duke research pro-
totype [30] was clinically evaluated in a study
involving eight patients undergoing surgery for
macular holes, epiretinal membranes, and vit-
reomacular traction [32]. The results confirmed
the ability to observe surgically induced chan-
ges in retinal contour and macular hole con-
figuration. The ability to acquire OCT images
simultaneously through the microscope over-
came a major limitation of a separate external
large imaging probe by eliminating the need for
frequent pauses during surgery. Commercial
systems are now available with the first being
the Zeiss RESCAN 700. Increases in imaging
speed combined with improved computation
using graphics processing units (GPUs) have
enabled real-time 3D [72] and 4D [73, 74]
intraoperative OCT. This provides improved
feedback on instrument position. Real-time
adjustments of the OCT focus to maintain par-
focality with the surgical microscope at differ-
ent axial positions and zoom levels is possible
[41]. Improved visualization includes heads-up
display (HUD) technology that adds OCT visu-
alization into the microscope ocular view [45]
to project OCT cross-sections [42] onto the
surgical field. Carrasco-Zevallos et al. demon-
strated volumetric 4D OCT data for real-time
surgical feedback [73, 75]. Others are examining
displaying images on virtual reality (VR) plat-
forms and gradually OCT has been added to
several robotic systems as reported in the fol-
lowing section.
Adv Ther (2021) 38:2114–2129
ROBOTIC SYSTEMS
FOR VITREORETINAL PROCEDURES
To address the host of complications with vit-
reoretinal surgery the literature presents several
types of robotic systems with an array of fea-
tures offering surgical advantages. These robotic
systems fall into four categories distinguished
by their interaction with the surgeon: (1)
handheld, (2) telemanipulated, (3) hand-on-
hand, and (4) magnetically controlled systems.
Handheld Systems for Vitreoretinal
Procedures
Handheld robotic surgical tools have been
explored to address the challenges of physio-
logic tremor and force perception with minimal
disruption to the surgical workflow. One
example of a handheld robotic surgical device is
Micron [7, 76]. Micron is a vitreoretinal surgical
tool designed to sense a surgeon’s tremor and
distinguish those movements from intentional
motion. It leverages the effects of constructive
and destructive interaction of wave signals to
filter the user’s tremor from the tool tip. The
device senses the user’s movements and iden-
tifies tremor as any input signal within the
8–12 Hz frequency band as determined else-
where [5]. To stabilize the surgical tool, piezo-
electric actuators direct Micron’s tool tip in a
direction opposite and equal in magnitude to
the tremor. Becker et al. [76] (Fig. 1i) improved
on the target acquisition of Micron by adding
image guidance. Two cameras were attached
directly to a surgical microscope as a stereo pair
for registering the tool tip’s location and to
measure the tool’s lateral displacement relative
to target vessels. The displacement data is used
as an additional feedback signal in combination
with the user’s movements to achieve 63%
success in experimental vessel cannulation as
shown in Fig. 1ii.
Force sensing was introduced by Gonenc
et al. [77] using fiber Bragg grating (FBG) strain
sensors to enable force sensing at the tool tip
following the design from Iordachita et al.’s [78]
vitreoretinal tool with a 0.25 mN resolution
(5.6 9 10-5 lb). The sensors are located at the
Adv Ther (2021) 38:2114–2129
Fig. 1 i An active surgical tool, Micron, that senses a user’s
tremor during manual microsurgeries and cancels the
effects of tremor on tool tip trajectory using piezoelectric
actuators for procedures such as retinal vein cannulation. ii
The improvement of tool tip trajectory during manual
tool’s tip to isolate retinal forces from the scle-
rotomy interaction forces, thereby inhibiting
the user from imposing damaging forces on the
retina. Yang et al. [79] optimized the Micron’s
design to allow six DOFs with a 4-mm-diameter
hemispherical workspace by using a parallel
actuator architecture offering more robust tre-
mor control. Yang et al. [80] used the six-DOF
Micron to demonstrate the advantage of using
tremor stabilization in acquiring clear B-mode
and C-mode OCT image acquisition and pre-
sented a precursor of a clinical tool capable of
tremor filtration paired with the visual feedback
capabilities of OCT.
The Integrated Robotic Intraocular Snake or
IRIS, developed by He et al. [25], is a robotic
surgical tool prototype offering surgeons
intraocular dexterity that is meant to be a
handheld device or a mountable attachment to
a robotic platform. IRIS was designed to match
the sizing of 20-gauge ophthalmic surgical tools
with a 0.9 mm outer diameter. The continuum
segment of the IRIS is 10 mm long and has two
rotational DOFs each with ± 45° of bending.
The linear actuators of the IRIS exhibited large
backlash and low actuation resolution which
limited the realizable precision of the final
design.
2119
manipulation with the inclusion of visual feedback to
Micron (Figures reproduced with permission from Becker
et al. [76])
Telemanipulation Robotic Systems
for Vitreoretinal Procedures
Wei et al. [12, 22] presented a multiplatform
robotic system in Fig. 2 that can manipulate the
eyeball and offer intraocular dexterity via a
bending continuum robot capable of deploying
microstents or grippers. The system allows for a
software-controlled remote center of motion
(RCM). The robotic arms of this system have
been demonstrated to enable deployment of
microstents in chorioallantoic chick mem-
branes [24] and were integrated with OCT for
control feedback [20] (Fig. 3).
Yu et al. [19] developed surgical forceps
shown in Fig. 4 integrated with a B-mode for-
ward-imaging OCT probe enabling real-time
intraocular imaging to improve accuracy for
membrane peeling procedures. The forceps were
made with a 25-gauge stainless steel (SS) tube
within a 23-gauge SS tube. The outer tube slides
along the 25-gauge tube forcing the opening
and closing of the forceps. The group showed
that integration of the custom OCT forceps with
the robot manipulator improved accuracy and
reduced the number of attempts needed to
accomplish a membrane peeling procedure.
Their results also emphasized the importance of
2120
Fig. 2 A two-arm parallel robot used for vitreoretinal operations that allow eye maneuvering and intraocular dexterity
(Figure courtesy of Nabil Simaan)
Fig. 3 A nine-DOF robot with parallel actuation platform
carrying a stenting robot capable of maneuvering with
precision better than 5 lm (Photo courtesy of Nabil
Simaan)
proximity of the OCT image monitor to the
surgeon to minimize head and eye movements
of the user.
Nasseri et al. developed a six-DOF miniature
robot [81] (Fig. 5). This robot creates linear and
rotational motion using two parallel prismatic
joints. There are two advantages of such a par-
allel mechanism. First the overall stiffness is
greater than what would be possible with seri-
ally linked actuators. The second advantage is
Adv Ther (2021) 38:2114–2129
the increased DOFs enabled with two separate
actuators. This six-DOF robot creates a highly
dexterous system eliminating a surgeon’s tre-
mor input and minimizing the effect of user
fatigue; however, challenges associated with
intraocular maneuverability are not addressed.
The Preceyes Surgical Robotic System was
developed for microintraocular procedures like
retinal vein cannulation and internal limiting
membrane peeling. The Preceyes system has a
motion controller that the surgeon uses to
command surgical tool tip position. The surgi-
cal tool is attached to a parallelogram manipu-
lator that enables operation around an RCM. By
setting a virtual point, at the sclerotomy,
around which a tool will rotate provides
advantages for the user. First, minimized inter-
action forces between the surgical tool and
sclerotomy mitigate any scleral trauma; second,
the orientation of the orbit remains unaffected,
which maintains line of site to the surgeon. The
group has also integrated the system with
external OCT imaging to establish tool tip
boundaries aiding the user in tool manipulation
and preventing inadvertent retinal contact or
puncture [82].
Adv Ther (2021) 38:2114–2129
Fig. 4 OCT-forceps with OCT fiber embedded in the 25-gauge stainless steel tube (SST). External actuation causes the
23-gauge SST to slide axially on the 25-gauge SST causing opening–closing of the forceps (Photo courtesy of Karen Joos)
Fig. 5 A hybrid parallel-serial surgical cooperative robot
capable of microscale motion using piezo actuators
(Figure reproduced with permission from Nasseri et al.
[81])
Gijbels et al. [83] developed a telemanipu-
lated robotic system to aid in retinal vein can-
nulation and epiretinal membrane peeling and
achieved successful in vivo human retinal vein
cannulation [84]. By enabling axial translation
as in Gijbels et al. [83], the size of tooling
around the eye was minimized and the robot
workspace for maneuvering around the micro-
scope viewing cone was maximized. Wilson
et al. [85] also developed a unique telemanipu-
lated intraocular robotic interventional surgical
system (IRISS) with two manipulators that
mount and travel on semicircular tracks. The
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tracks can be independently positioned with
two separate actuators to allow six DOFs of
surgical tool manipulation. Each tool is kine-
matically constrained to a fixed RCM defined by
the device geometry. The IRISS was tested on
cadaver porcine eyes to demonstrate retinal
vein cannulation and for cataract extraction.
The group also tested the feasibility of using
OCT for calibrating the RCM point and con-
cluded that RCM alignment using visible red
dot lasers may introduce deviations too large for
full autonomy.
Del Giudice et al. [86, 87] developed con-
tinuum robots for multiscale motion (CREM)
demonstrating a novel concept for teleoperated
robot actuation for surgeries requiring micro-
scale motion like microvascular reconstruction
and image-based (OCT) diagnosis. The CREM
robot is capable of maneuvering tools within
both macro- and micro-workspaces with a
positional resolution of 1 lm. It was shown that
3D OCT images may be obtained by using the
robot’s micromotion capability while carrying a
B-mode OCT probe, which was an adaptation
from Shen et al. [88]. In addition to validating
3D OCT on a cadaveric porcine retina, closed-
loop control and OCT-guided visual servoing at
the micromotion scale was also demonstrated
for targeting a needle into a microchannel.
While this system was not miniaturized to
operate within the eye, the same design concept
may be used for high-precision and low-cost
2122
robotic devices for manipulating needles within
the eye with OCT feedback.
Hand-on-Hand Robotic Systems
for Vitreoretinal Procedures
By minimizing positioning error of a tool tip
caused by human tremor, some active surgical
tools enable microsurgeries that are impossible
with traditional surgical tools. Maneuvering
handheld robotic tools for microsurgeries still
requires a tremendous level of skill, however, as
the level of tremor filtration is limited by the
stroke magnitude of the device’s actuators. Like
telemanipulated robots, hand-on-hand robots
offer a greater advantage of tremor filtration by
leveraging the mechanical stiffness of robotic
systems to drive surgical tools in tandem with
the surgeon.
Hand-on-hand robotic systems allow the
surgeon to drive a tool mounted on a robotic
platform using force input commands. This
approach has several advantages in terms of
reduced cost and ease of clinical deployment. In
addition, the robot can be used for tremor fil-
tering, for position recall, and for reducing
surgeon fatigue since the robot can hold the
Fig. 6 i An early iteration of a cooperative surgical robot,
the Steady-Hand Robot with robotic platform and surgical
tool attached to a six-DOF force sensor for robot control
(Photo courtesy of Russell H. Taylor and Iulian I.
Iordachita). ii An iteration of the Steady-Hand Robot,
Adv Ther (2021) 38:2114–2129
tool at a fixed position even if the surgeon lets
go of it.
The Steady-Hand Robot [10] and Steady-
Hand Robot 2 [89], shown in Fig. 6, were
developed to augment a surgeon’s capabilities
with retinal and other microsurgeries in mind.
The Steady-Hand is a cooperative robotic sys-
tem, where the surgeon and a robotic actuator
simultaneously control a surgical tool. The sur-
geon manipulates surgical tools in the same
fashion as traditional tools with the robot con-
troller reading force signals from the surgeon’s
hand movements to drive the robot. The robot
is capable of producing smooth, natural motion
profiles that a surgeon would typically use dur-
ing retinal procedures while eliminating the
extraneous tool movements that result from
tremor.
The first realization of the Steady-Hand from
Taylor et al. [10] improved success of needle
insertion into a hole 150 lm in diameter by
36% [90] when compared to manual needle
insertion. Balicki et al. [18] used a custom
25-gauge surgical pick with integrated OCT for
epiretinal membrane peeling. With the OCT
surgical pick providing visual feedback, the
Steady-Hand was able to maintain a specified
distance of the surgical tool tip from retinal
the Steady-Hand Robot 2, or Eye Robot 2 (ER2). (Fig-
ure reproduced with permission from Üneri et al. [10])
Adv Ther (2021) 38:2114–2129
tissue to within 10 lm of a desired 150 lm. The
OCT imaging enabled identification of struc-
tures beyond surface layers as targets that can be
used to guide tool puncturing tasks while lim-
iting puncture depths. Üneri et al. [89] evolved
the Steady-Hand by including a force sensor
attached to the surgical tool. The additional
sensor provides applied tool forces as feedback
data to the robot controller to limit maximum
forces applied to intraocular tissue. The force
feedback data aids in guiding surgeons to avoid
unintended destructive contact and, like the
OCT feedback, is used to maintain tool posi-
tioning with respect to intraocular anatomy.
The combined inputs from the OCT imaging
and force sensor optimize tool trajectory, for
instance, while maintaining tool angle during a
Fig. 7 The extraocular magnetic field generating system,
OctoMag, capable of guiding magnetic drug-eluting
microcapsules and magnetic tip microcannula in five
DOFs, i.e., three degrees of positional control and two
orientational degrees (Figure courtesy of Bradley Nelson
and MagnebotiX AG, Zurich, Switzerland)
2123
peeling motion that minimizes resistance to
limit membrane tearing.
Magnetically Controlled Robot Systems
Finally, other approaches using magnetically
controlled microrobots have been explored over
the past decade. These systems utilize an
extraocular magnetic field to control robotic
microcapsules within the eye for procedures like
retinal vein cannulation and localized drug
delivery using drug-eluting microcapsules.
Kummer et al. [15] used a magnetic field system
called the OctoMag (Fig. 7) to guide a micro-
capsule robot in five DOFs, i.e., three degrees of
positional control and two orientational
degrees. One of the advantages of magnetic
systems is achieving high levels of intraocular
dexterity and maneuverability without physical
attachment to the extraocular space [15]. Min-
imizing attachments between the extraocular
and intraocular space eliminates the eye
manipulability constraints imposed by pars
plana sclerotomy surgical tools and maximizes
the degrees of manipulation available for the
line of site of intraocular anatomy. These
advantages, however, come at the expense of
very complex magnetic field generators that
encompass a large portion of the space around
the patient’s head.
Charreyron et al. [16, 17] used the OctoMag
magnetic field system to drive a magnetic tip
microcannula for delivery of gene therapy
injections to subretinal tissue. The group
developed semiautonomous control that auto-
matically aligns the tool magnetic field to keep
the tool tip perpendicular to the retinal surface
at a target site identified by the surgeon. The
user, while following tool manipulation
through the microscope, determines when the
tool tip is optimally placed for injection. Mag-
netic microcannulas maintain the advantages
of intraocular dexterity that characterize
microcapsule robots by relying solely on the
magnetic field for actuation. These magnetic
manipulators also offer a potential safety
advantage over traditional rigid surgical tools
because of their limited rigidity and limitations
of achievable forces. The group explored the
2124
feasibility of autonomous control and also
explored OCT imaging for improved tool tip
tracking. Their system exhibits 11 degrees of
angular error of the magnetic field in a worst-
case scenario which translates to 4.2 mm of
displacement of a 21-mm-long cannula. For full
autonomous control to be clinically realizable,
precision of magnetic field alignment will be
necessary
DISCUSSION
Vitreoretinal surgical techniques and available
procedures are in a transitional state due to the
contributions of advanced visualization tech-
niques and the development of robotic surgical
devices. The future of vitreoretinal surgery is the
possible realization of autonomy for an array of
procedures available today, but more impor-
tantly, enabling procedures that are not cur-
rently available because of human physiological
limitations. For instance, gene therapy injec-
tions require the utmost precision for target
acquisition. Magnetic field generators guide
magnetic drug-eluting microrobots enabling
intraocular drug injections. Magnetic intraocu-
lar robots eliminate the pars plana sclerotomy
manipulation constraints but require a large
volume of the workspace surrounding the
patient’s head. An alternative approach for tar-
geting is OCT imaging which delivers high-
definition images necessary for intraocular
navigation. When OCT imaging is paired with
robotic platforms as a feedback modality, the
combined system can drive tools to specific
retinal locations with improved accuracy and
reduced dependence upon human surgical
skills.
Some of the robotic systems mentioned are
already in a developmental stage where auton-
omy is possible. The Steady-Hand robot, for
instance, demonstrated autonomous manipu-
lation of a needle inserted into a 150–250 lm
hole, improving success of insertion by an
average of 31.8% compared to handheld inser-
tions. With added OCT imaging, performing
vitreoretinal tasks expands further to assist in
manipulation of semitransparent membranes
and target subsurface tissue. Depending solely
Adv Ther (2021) 38:2114–2129
on OCT visual feedback, the robot controller
can bypass the force input from a user to drive
surgical tools to locations identified with the
OCT. By utilizing distance measurement capa-
bilities of OCT or force guidance with FBG
integrated tool tips, the likelihood of tissue
damaging contact is reduced.
With a system like CREM, tasks requiring
ultra-precision and autonomous intervention
are possible with miniaturization of the tech-
nology. Utilizing equilibrium modulation as an
actuation technique enables robotics in surgery
to carry out microscale tasks with much finer
positional adjustments than other robots. Fur-
ther, enabling these micromanipulation tasks
does not sacrifice the capabilities in the macro-
workspace enabling a greater number of surgical
tasks.
Although surgical robots have shown their
capabilities in advancing vitreoretinal surgery,
they are not without limitations. Developing
OCT-guided robotic tools that do not disrupt
the clinical workflow requires hardware capable
of high sampling frequencies allowing for
improved OCT image quality via filtering and
multiframe averaging techniques. Registration
of the OCT probe image frame to the robot
frame is challenging—especially for systems
using an external OCT. Stabilization of the
robotic tool relative to the patient head (or use
of active eye motion tracking) are key to
enhancing safety. Finally, the ability to achieve
fast and safe tool retraction in case of involun-
tary ocular movements or in case of a clinical
emergency will be paramount to safe clinical
deployment.
CONCLUSIONS
Clinical surgical robotics will likely use tech-
nologies like OCT and tool tip force measure-
ments to enhance the surgeon’s perception and
accuracy. These robotic systems will include
powerful control computers, particularly those
using OCT, with calibration methods and con-
trol algorithms accounting for safe anatomical
movements during procedures. The future of
vitreoretinal surgery may include some of the
robotic systems or implementations of
Adv Ther (2021) 38:2114–2129
technology introduced in the development of
the robots discussed in this review.
This review article is based on previously
conducted studies and does not contain any
new studies with human participants or animals
performed by any of the authors.
ACKNOWLEDGEMENTS
Funding. This work was supported in part by
the National Institute of Health National Eye
Institute (NEI/NIH) grant 1R01EY028133 (KMJ,
NS), in part by The National Science Foundation
grant CMMI-1537659 (NS, KMJ), in part by the
Joseph Ellis Family and William Black Research
Funds (KMJ), in part by the Unrestricted
Departmental Grant to the Vanderbilt Eye
Institute from Research to Prevent Blindness,
Inc., NY (KMJ). No Rapid Service Fee was
received by the journal for the publication of
this article.
Authorship. All named authors meet the
International Committee of Medical Journal
Editors (ICMJE) criteria for authorship for this
article, take responsibility for the integrity of
the work as a whole, and have given their
approval for this version to be published.
Disclosures. Elan Ahronovich declares that
he has no conflict of interest. Nabil Simaan and
Karen Joos have received funding from NEI/NIH
and NSF.
Compliance with Ethics Guidelines. This
review article is based on previously conducted
studies and does not contain any new studies
with human participants or animals performed
by any of the authors.
Data Availability. Data sharing is not
applicable to this article as no datasets were
generated or analyzed during this review article.
Open Access. This article is licensed under a
Creative Commons Attribution-NonCommer-
cial 4.0 International License, which permits
any non-commercial use, sharing, adaptation,
2125
distribution and reproduction in any medium
or format, as long as you give appropriate credit
to the original author(s) and the source, provide
a link to the Creative Commons licence, and
indicate if changes were made. The images or
other third party material in this article are
included in the article’s Creative Commons
licence, unless indicated otherwise in a credit
line to the material. If material is not included
in the article’s Creative Commons licence and
your intended use is not permitted by statutory
regulation or exceeds the permitted use, you
will need to obtain permission directly from the
copyright holder. To view a copy of this licence,
visit http://creativecommons.org/licenses/by-
nc/4.0/.
REFERENCES
1. Machemer R. Vitrectomy, a pars plana approach.
Trans Am Acad Ophthalmol. 1971;75:813–20.
2. Jagtap AD, Riviere CN. Applied force during vitre-
oretinal microsurgery with handheld instruments.
In: The 26th annual international conference of the
IEEE engineering in medicine and biology society,
vol. 1. IEEE; 2004. pp. 2771–2773.
3. Jensen P, Gupta P, De Juan E. Quantification of
microsurgical tactile perception. In: Proceedings of
the first joint BMES/EMBS conference. 1999 IEEE
engineering in medicine and biology 21st annual
conference and the 1999 annual fall meeting of the
biomedical engineering society, vol. 2. IEEE; 1999.
p. 839.
4. Wilkins JR, Puliafito CA, Hee MR, et al. Character-
ization of epiretinal membranes using optical
coherence tomography. Ophthalmology.
1996;103(12):2142–51.
5. Riviere CN, Rader RS, Khosla PK. Characteristics of
hand motion of eye surgeons. In: Proceedings of the
19th annual international conference of the IEEE
engineering in medicine and biology society ‘Mag-
nificent Milestones and Emerging Opportunities in
Medical Engineering’ (Cat. No. 97CH36136), vol. 4.
IEEE; 1997. pp. 1690–1693.
6. Singh S, Riviere C. Physiological tremor amplitude
during retinal microsurgery. In: Proceedings of the
IEEE 28th annual northeast bioengineering confer-
ence (IEEE Cat. No. 02CH37342). IEEE; 2002. pp.
171–172.
2126
7. Riviere CN, Ang WT, Khosla PK. Toward active
tremor canceling in handheld microsurgical
instruments. IEEE Trans Robot Autom. 2003;19(5):
793–800.
8. Song C, Gehlbach PL, Kang JU. Active tremor can-
cellation by a ‘‘smart’’ handheld vitreoretinal
microsurgical tool using swept source optical
coherence tomography. Opt Express. 2012;20(21):
23414–21.
9. Cheon GW, Huang Y, Kang JU. Active depth-lock-
ing handheld micro-injector based on common-
path swept source optical coherence tomography.
In: Optical fibers and sensors for medical diagnos-
tics and treatment applications XV, vol. 9317.
International Society for Optics and Photonics;
2015. p. 93170U.
10. Taylor R, Jensen P, Whitcomb L, et al. A steady-
hand robotic system for microsurgical augmenta-
tion. Int J Robot Res. 1999;18(12):1201–10.
11. Charles S. Dexterity enhancement in microsurgery
using telemicro-robotics. In: Medicine meets virtual
reality II, interactive technology and healthcare:
visionary applications for simulation, visualization,
robotics; 1994.
12. Wei W, Goldman R, Simaan N, Fine H, Chang S.
Design and theoretical evaluation of microsurgical
manipulators for orbital manipulation and
intraocular dexterity. In: Proceedings 2007 IEEE
international conference on robotics and automa-
tion. IEEE; 2007. pp. 3389–3395.
13. Yu H, Shen JH, Joos KM, Simaan N. Design, cali-
bration and preliminary testing of a robotic tele-
manipulator for OCT guided retinal surgery. In:
2013 IEEE international conference on robotics and
automation. IEEE; 2013. pp. 225–231.
14. Meenink T, Naus G, de Smet M, Beelen M, Stein-
buch M. Robot assistance for micrometer precision
in vitreoretinal surgery. Investig Ophthalmol Vis
Sci. 2013;54(15):5808–5808.
15. Kummer MP, Abbott JJ, Kratochvil BE, Borer R,
Sengul A, Nelson BJ. OctoMag: an electromagnetic
system for 5-DOF wireless micromanipulation. IEEE
Trans Robot. 2010;26(6):1006–17.
16. Charreyron SL, Zeydan B, Nelson BJ. Shared control
of a magnetic microcatheter for vitreoretinal tar-
geted drug delivery. In: ICRA; 2017. pp. 4843–4848.
17. Charreyron SL, Boehler Q, Danun A, Mesot A,
Becker M, Nelson BJ. A magnetically navigated
microcannula for subretinal injections. In: IEEE
transactions on biomedical engineering. 2020.
Adv Ther (2021) 38:2114–2129
18. Balicki M, Han JH, Iordachita I, et al. Single fiber
optical coherence tomography microsurgical
instruments for computer and robot-assisted retinal
surgery. In: International conference on medical
image computing and computer-assisted interven-
tion. Springer; 2009. pp. 108–115.
19. Yu H, Shen JH, Shah RJ, Simaan N, Joos KM. Eval-
uation of microsurgical tasks with OCT-guided and/
or robot-assisted ophthalmic forceps. Biomed Opt
Express. 2015;6(2):457–72.
20. Yu H, Shen JH, Joos KM, Simaan N. Calibration and
integration of B-mode optical coherence tomogra-
phy for assistive control in robotic microsurgery.
IEEE ASME Trans Mechatron. 2016;21(6):2613–23.
21. Ikuta K, Kato T, Nagata S. Development and
experimental verification of micro active forceps for
microsurgery. In: MHS’96 proceedings of the sev-
enth international symposium on micro machine
and human science. IEEE; 1996. pp. 229–234.
22. Wei W, Goldman RE, Fine HF, Chang S, Simaan N.
Performance evaluation for multi-arm manipula-
tion of hollow suspended organs. IEEE Trans Robot.
2008;25(1):147–57.
23. Simaan N, Taylor RH, Handa JT. System and
method for macro-micro distal dexterity enhance-
ment in micro-surgery of the eye. Google Patents;
2019. US Patent 10,406,026.
24. Wei W, Popplewell C, Chang S, Fine HF, Simaan N.
Enabling technology for microvascular stenting in
ophthalmic surgery. J Med Devices. 2010;4(1):
014503.
25. He X, Van Geirt V, Gehlbach P, Taylor R, Iordachita
I. IRIS: integrated robotic intraocular snake. In:
2015 IEEE international conference on robotics and
automation (ICRA). IEEE; 2015. pp. 1764–1769.
26. Song J, Gonenc B, Guo J, Iordachita I. Intraocular
snake integrated with the steady-hand eye robot for
assisted retinal microsurgery. In: 2017 IEEE inter-
national conference on robotics and automation
(ICRA). IEEE; 2017. pp. 6724–6729.
27. Dayani PN, Maldonado R, Farsiu S, Toth CA.
Intraoperative use of handheld spectral domain
optical coherence tomography imaging in macular
surgery. Retina. 2009;29(10):1457.
28. Binder S, Falkner-Radler CI, Hauger C, Matz H,
Glittenberg C. Feasibility of intrasurgical spectral-
domain optical coherence tomography. Retina.
2011;31(7):1332–6.
29. Hahn P, Migacz J, O’Connell R, Izatt JA, Toth CA.
Unprocessed real-time imaging of vitreoretinal
surgical maneuvers using a microscope-integrated
Adv Ther (2021) 38:2114–2129
spectral-domain optical coherence tomography
system. Graefe’s Arch Clin Exp Ophthalmol.
2013;251(1):213–20.
30. Tao YK, Ehlers JP, Toth CA, Izatt JA. Intraoperative
spectral domain optical coherence tomography for
vitreoretinal surgery. Opt Lett. 2010;35(20):3315–7.
31. Pasricha ND, Shieh C, Carrasco-Zevallos OM, et al.
Real-time microscope-integrated OCT to improve
visualization in DSAEK for advanced bullous ker-
atopathy. Cornea. 2015;34(12):1606.
32. Hahn P, Migacz J, O’Connell R, et al. Preclinical
evaluation and intraoperative human retinal
imaging with a high-resolution microscope-inte-
grated spectral domain optical coherence tomog-
raphy device. Retina. 2013;33(7):1328.
33. Hahn P, Carrasco-Zevallos O, Cunefare D, et al.
Intrasurgical human retinal imaging with manual
instrument tracking using a microscope-integrated
spectral-domain optical coherence tomography
device. Transl Vis Sci Technol. 2015;4(4):1–1.
34. Ehlers JP, Tao YK, Farsiu S, Maldonado R, Izatt JA,
Toth CA. Integration of a spectral domain optical
coherence tomography system into a surgical
microscope for intraoperative imaging. Investig
Ophthalmol Vis Sci. 2011;52(6):3153–9.
35. Hahn P, Migacz J, O’Connell R, Maldonado RS, Izatt
JA, Toth CA. The use of optical coherence tomog-
raphy in intraoperative ophthalmic imaging. Oph-
thalmic Surg Lasers Imaging Retina. 2011;42(4):
S85–94.
36. Ehlers J. Intraoperative optical coherence tomog-
raphy: past, present, and future. Eye. 2016;30(2):
193–201.
37. Ehlers JP, Tao YK, Farsiu S, Maldonado R, Izatt JA,
Toth CA. Visualization of real-time intraoperative
maneuvers with a microscope-mounted spectral
domain optical coherence tomography system.
Retina. 2013;33(1):232.
38. Grewal DS, Bhullar PK, Pasricha ND, et al. Intraop-
erative 4D microscope-integrated optical coherence
tomography guided 27-gauge transvitreal reti-
nochoroidal biopsy for choroidal melanoma.
Retina. 2017;37(4):796.
39. Ehlers JP, McNutt S, Dar S, Tao YK, Srivastava SK.
Visualisation of contrast-enhanced intraoperative
optical coherence tomography with indocyanine
green. Br J Ophthalmol. 2014;98(11):1588–91.
40. Ehlers JP, Tao YK, Srivastava SK. The value of
intraoperative OCT imaging in vitreoretinal sur-
gery. Curr Opin Ophthalmol. 2014;25(3):221.
2127
41. Tao YK, Srivastava SK, Ehlers JP. Microscope-inte-
grated intraoperative OCT with electrically tunable
focus and heads-up display for imaging of oph-
thalmic surgical maneuvers. Biomed Opt Express.
2014;5(6):1877–85.
42. Ehlers JP, Srivastava SK, Feiler D, Noonan AI, Rollins
AM, Tao YK. Integrative advances for OCT-guided
ophthalmic surgery and intraoperative OCT:
microscope integration, surgical instrumentation,
and heads-up display surgeon feedback. PLoS One.
2014;9(8):e105224.
43. El-Haddad MT, Tao YK. Automated stereo vision
instrument tracking for intraoperative OCT guided
anterior segment ophthalmic surgical maneuvers.
Biomed Opt Express. 2015;6(8):3014–31.
44. Ehlers JP, Han J, Petkovsek D, Kaiser PK, Singh RP,
Srivastava SK. Membrane peeling-induced retinal
alterations on intraoperative OCT in vitreomacular
interface disorders from the PIONEER study.
Investig Ophthalmol Vis Sci. 2015;56(12):7324–30.
45. Ehlers JP, Goshe J, Dupps WJ, et al. Determination
of feasibility and utility of microscope-integrated
optical coherence tomography during ophthalmic
surgery: the DISCOVER Study RESCAN Results.
JAMA Ophthalmol. 2015;133(10):1124–32.
46. Cost B, Goshe JM, Srivastava S, Ehlers JP. Intraop-
erative optical coherence tomography-assisted
Descemet membrane endothelial keratoplasty in
the DISCOVER study. Am J Ophthalmol.
2015;160(3):430–7.
47. Ehlers JP, Uchida A, Srivastava SK. Intraoperative
optical coherence tomography-compatible surgical
instruments for real-time image-guided ophthalmic
surgery. Br J Ophthalmol. 2017;101(10):1306–8.
48. Malone JD, El-Haddad MT, Bozic I, et al. Simulta-
neous multimodal ophthalmic imaging using
swept-source spectrally encoded scanning laser
ophthalmoscopy and optical coherence tomogra-
phy. Biomed Opt Express. 2017;8(1):193–206.
49. Lytvynchuk L, Glittenberg C, Binder S. Intraopera-
tive spectral domain optical coherence tomogra-
phy: technology, applications, and future
perspectives. In: Meyer C, Saxena S, Sadda S, edi-
tors. Spectral domain optical coherence tomogra-
phy in macular diseases. New Delhi: Springer; 2017.
pp. 423–443.
50. Binder S, Falkner-Radler C, Hauger C, Matz H,
Glittenberg C. Clinical applications of intrasurgical
SD-optical coherence tomography. Investig Oph-
thalmol Vis Sci. 2010;51(13):268–268.
2128
51. Matz H, Binder S, Glittenberg C, et al. Intraopera-
tive applications of OCT in ophthalmic surgery.
Biomed Eng. 2012;57(SI-1 Track-P):297–297.
52. Maier MM, Nasseri A, Framme C, Bohnacker S,
Becker MD, Heinrich D, et al. Die intraoperative
optische Kohärenztomografie in der Netzhaut-
Glaskörper-Chirurgie. Aktuelle Erfahrungen und
Ausblick auf künftige Entwicklungsschritte. Klin
Monbl Augenheilkd. 2018;235(09):1028–34.
53. Carrasco-Zevallos OM, Viehland C, Keller B, et al.
Review of intraoperative optical coherence tomog-
raphy: technology and applications. Biomed Opt
Express. 2017;8(3):1607–37.
54. Sasahara M, Kiryu J, Yoshimura N. Endoscope-as-
sisted transscleral suture fixation to reduce the
incidence of intraocular lens dislocation. J Cataract
Refract Surg. 2005;31(9):1777–80.
55. Tarantola RM, Agarwal A, Lu P, Joos KM. Long-term
results of combined endoscope-assisted pars plana
vitrectomy and glaucoma tube shunt surgery.
Retina. 2011;31(2):275.
56. Olsen TW, Pribila JT. Pars plana vitrectomy with
endoscope-guided sutured posterior chamber
intraocular lens implantation in children and
adults. Am J Ophthalmol. 2011;151(2):287–96.
57. Al Sabti K, Raizada S. Endoscope-assisted pars plana
vitrectomy in severe ocular trauma. Br J Ophthal-
mol. 2012;96(11):1399–403.
58. Maeda M, Watanabe M, Ichikawa K.
Goniosynechialysis using an ophthalmic endo-
scope and cataract surgery for primary angle-closure
glaucoma. J Glaucoma. 2014;23(3):174–8.
59. Kawashima S, Kawashima M, Tsubota K. Endo-
scopy-guided vitreoretinal surgery. Expert Rev Med
Devices. 2014;11(2):163–8.
60. Francis BA, Kwon J, Fellman R, et al. Endoscopic
ophthalmic surgery of the anterior segment. Surv
Ophthalmol. 2014;59(2):217–31.
61. Li J, Quirk BC, Noble PB, Kirk RW, Sampson DD,
McLaughlin RA. Flexible needle with integrated
optical coherence tomography probe for imaging
during transbronchial tissue aspiration. J Biomed
Opt. 2017;22(10):106002.
62. Iftimia NV, Bouma BE, Pitman MB, Goldberg B,
Bressner J, Tearney GJ. A portable, low coherence
interferometry based instrument for fine needle
aspiration biopsy guidance. Rev Sci Instrum.
2005;76(6):064301.
63. Li Z, Shen JH, Kozub JA, Prasad R, Lu P, Joos KM.
Miniature forward-imaging B-scan optical
Adv Ther (2021) 38:2114–2129
coherence tomography probe to guide real-time
laser ablation. Lasers Surg Med. 2014;46(3):
193–202.
64. Joos KM, Shen JH. Miniature real-time intraopera-
tive forward-imaging optical coherence tomogra-
phy probe. Biomed Opt Express. 2013;4(8):1342–50.
65. Joos KM, Shen JH. Preliminary design and evalua-
tion of a B-scan OCT-guided needle. Photonics.
2014;1:260–266.
66. Ray R, Barañano DE, Fortun JA, et al. Intraoperative
microscope-mounted spectral domain optical
coherence tomography for evaluation of retinal
anatomy during macular surgery. Ophthalmology.
2011;118(11):2212–7.
67. Branchini LA, Gurley K, Duker JS, Reichel E. Use of
handheld intraoperative spectral-domain optical
coherence tomography in a variety of vitreoretinal
diseases. Ophthalmic Surg Lasers Imaging Retina.
2016;47(1):49–54.
68. Ehlers JP, Dupps WJ, Kaiser PK, et al. The prospec-
tive intraoperative and perioperative ophthalmic
imaging with optical coherence tomography (PIO-
NEER) study: 2-year results. Am J Ophthalmol.
2014;158(5):999–1007.
69. De Benito-Llopis L, Mehta JS, Angunawela RI, Ang
M, Tan DT. Intraoperative anterior segment optical
coherence tomography: a novel assessment tool
during deep anterior lamellar keratoplasty. Am J
Ophthalmol. 2014;157(2):334–41.
70. Carrasco-Zevallos O, Keller B, Viehland C, et al. 4D
microscope-integrated OCT improves accuracy of
ophthalmic surgical maneuvers. In: Ophthalmic
technologies XXVI, vol. 9693. International Society
for Optics and Photonics; 2016. p. 969306.
71. Todorich B, Shieh C, DeSouza PJ, et al. Impact of
microscope-integrated OCT on ophthalmology
resident performance of anterior segment surgical
maneuvers in model eyes. Investig Ophthalmol Vis
Sci. 2016;57(9):OCT146–53.
72. Wieser W, Draxinger W, Klein T, Karpf S, Pfeiffer T,
Huber R. High definition live 3D-OCT in vivo:
design and evaluation of a 4D OCT engine with 1
GVoxel/s. Biomed Opt Express. 2014;5(9):2963–77.
73. Carrasco-Zevallos O, Keller B, Viehland C, et al. Live
volumetric (4D) visualization and guidance of
in vivo human ophthalmic surgery with intraoper-
ative optical coherence tomography. Sci Rep.
2016;6:31689.
74. Viehland C, Keller B, Carrasco-Zevallos OM, et al.
Enhanced volumetric visualization for real time 4D
Adv Ther (2021) 38:2114–2129
intraoperative ophthalmic swept-source OCT.
Biomed Opt Express. 2016;7(5):1815–29.
75. Shen L, Carrasco-Zevallos O, Keller B, et al. Novel
microscope-integrated stereoscopic heads-up dis-
play for intrasurgical optical coherence tomogra-
phy. Biomed Opt Express. 2016;7(5):1711–26.
76. Becker BC, Voros S, Lobes LA, Handa JT, Hager GD,
Riviere CN. Retinal vessel cannulation with an
image-guided handheld robot. In: 2010 Annual
international conference of the IEEE engineering in
medicine and biology. IEEE; 2010. pp. 5420–5423.
77. Gonenc B, Balicki MA, Handa J, et al. Preliminary
evaluation of a micro-force sensing handheld robot
for vitreoretinal surgery. In: 2012 IEEE/RSJ inter-
national conference on intelligent robots and sys-
tems. IEEE; 2012. pp. 4125–4130.
78. Iordachita I, Sun Z, Balicki M, et al. A sub-milli-
metric, 0.25 mN resolution fully integrated fiber-
optic force-sensing tool for retinal microsurgery. Int
J Comput Assist Radiol Surg. 2009;4(4):383–90.
79. Yang S, MacLachlan RA, Riviere CN. Design and
analysis of 6 DOF handheld micromanipulator. In:
2012 IEEE international conference on robotics and
automation. IEEE; 2012. pp. 1946–1951.
80. Yang S, Balicki M, MacLachlan RA, et al. Optical
coherence tomography scanning with a handheld
vitreoretinal micromanipulator. In: 2012 Annual
international conference of the IEEE Engineering in
Medicine and Biology Society. IEEE; 2012. pp.
948–951.
81. Nasseri MA, Eder M, Eberts D, et al. Kinematics and
dynamics analysis of a hybrid parallel-serial micro-
manipulator designed for biomedical applications.
In: 2013 IEEE/ASME international conference on
advanced intelligent mechatronics. IEEE; 2013. pp.
293–299.
82. Maberley DA, Beelen M, Smit J, et al. A comparison
of robotic and manual surgery for internal limiting
membrane peeling. Graefe’s Arch Clin Exp Oph-
thalmol. 2020:258(4):773–8.
2129
83. Gijbels A, Vander Poorten EB, Stalmans P, Van
Brussel H, Reynaerts D. Design of a teleoperated
robotic system for retinal surgery. In: 2014 IEEE
international conference on robotics and automa-
tion (ICRA). IEEE; 2014. pp. 2357–2363.
84. Gijbels A, Smits J, Schoevaerdts L, et al. In-human
robot-assisted retinal vein cannulation, a world
first. Ann Biomed Eng. 2018;46(10):1676–85.
85. Wilson JT, Gerber MJ, Prince SW, et al. Intraocular
robotic interventional surgical system (IRISS):
mechanical design, evaluation, and master–slave
manipulation. Int J Med Robot Comput Assist Surg.
2018;14(1):e1842.
86. Del Giudice G, Wang L, Shen JH, Joos K, Simaan N.
Continuum robots for multi-scale motion: micro-
scale motion through equilibrium modulation. In:
2017 IEEE/RSJ international conference on intelli-
gent robots and systems (IROS). IEEE; 2017. pp.
2537–2542.
87. Del Giudice G, Orekhov A, Shen J, Joos K, Simaan
N. Investigation of micro-motion kinematics of
continuum robots for volumetric OCT and OCT-
guided visual servoing. IEEE/ASME Trans Mecha-
tron. 2020. https://doi.org/10.1109/TMECH.2020.
3043438.
88. Shen JH, Kozub J, Prasad R, Joos KM. An intraocular
OCT probe. Investig Ophthalmol Vis Sci.
2011;52(14):1326–1326.
89. Üneri A, Balicki MA, Handa J, Gehlbach P, Taylor
RH, Iordachita I. New steady-hand eye robot with
micro-force sensing for vitreoretinal surgery. In:
2010 3rd IEEE RAS and EMBS international confer-
ence on biomedical robotics and biomechatronics.
IEEE; 2010. pp. 814–819.
90. Kumar R, Goradia TM, Barnes AC, et al. Perfor-
mance of robotic augmentation in microsurgery-
scale motions. In: International conference on
medical image computing and computer-assisted
intervention. Springer; 1999. pp. 1108–1115.